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Palbociclib and endocrine therapy in heavily pretreated hormone receptor-positive HER2-negative advanced breast cancer: the UK Compassionate Access Programme experience

  • Nicolò Matteo Luca BattistiEmail author
  • Belinda KingstonEmail author
  • Judy King
  • Arshi Denton
  • Simon Waters
  • Ailsa Sita-Lumsden
  • Farah Rehman
  • Chara Stavraka
  • Hartmut Kristeleit
  • Elinor Sawyer
  • David Houghton
  • Neville Davidson
  • Sacha Howell
  • Julia Choy
  • Peter Harper
  • Rebecca Roylance
  • Raja Fharat
  • Kabir Mohammed
  • Alistair Ring
  • Stephen Johnston
Clinical trial

Abstract

Purpose

Palbociclib is approved in 1st line for hormone receptor (HR)-positive HER2-negative advanced breast cancer (ABC). A Compassionate Access Programme previously allowed patients to receive it in 4th line. However, Palbociclib has not been specifically tested in this population. We aimed to determine the safety and efficacy profile of Palbociclib within the Programme across ten institutions in the United Kingdom.

Methods

We retrospectively identified HR-positive HER2-negative ABC patients on the Programme between December 2015 and September 2017. Demographics, disease characteristics, prior treatments, blood tests, toxicities, treatment delays and responses were recorded. Simple statistics, Fisher’s exact test, χ2 method and Cox regression were used.

Results

118 patients identified had a median age of 59. 82.2% were postmenopausal and 92.4% performance status 0–1. 81.4% had visceral involvement and 6.8% bone-only disease after a median of 5 prior treatments and 3 prior chemotherapies. Clinical benefit rate was 47.5%, overall response rate 15.8%, median PFS 4.5 months and median OS 15.8 months. Longer progression-free survival on prior endocrine therapy was a predictor of longer PFS and OS. 89.7% developed neutropenia (grade ≥ 3 in 56.8%). 5.1% experienced febrile neutropenia. 48.3% had dose reductions and 3.4% discontinued Palbociclib following toxicity. No statistically significant difference in grade ≥ 3 neutropenia was observed according to metastatic sites nor previous treatments.

Conclusions

This is the most extensive analysis of palbociclib in ≥ 4th-line setting. Clinical benefit was confirmed particularly for endocrine-sensitive, predominantly bony disease and in earlier lines of treatment. Safety was similar to PALOMA trials with higher febrile neutropenia rate.

Keywords

Breast cancer ER-positive Palbociclib Advanced stage Pretreated 

Notes

Acknowledgements

The authors wish to acknowledge the support of Pfizer in providing a list of centres enrolling patients within the Compassionate Access Programme. Prof Johnston, Dr Ring, Dr Battisti and Dr Kingston wish to acknowledge the support of The Royal Marsden NIHR Biomedical Research Centre for Cancer.

Conflict of interest

Prof Johnston has received consulting and advisory board fees from Eli Lilly, AstraZeneca and Puma Biotechnology, speaker fees from Pfizer and Novartis and research funding from Pfizer. Dr Ring has received advisory board fees from Novartis, Pfizer and Lilly and speaker fees from Novartis and Pfizer. Dr Roylance has received an institutional educational grant from Pfizer and honoraria from Pfizer for advisory board and educational meetings. Dr Waters has received speaker and advisory fees from Genomic Health International, Novartis UK and Eisai Ltd. Dr Battisti, Dr Kingston, Dr Harper, Dr King, Dr Denton, Dr Sita-Lumsden, Dr Rehman, Dr Stavraka, Dr Kristeleit, Prof Sawyer, Dr Houghton, Prof Davidson, Dr Howell, Ms Choy, Dr Fharat and Mr Mohammed have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Nicolò Matteo Luca Battisti
    • 1
    Email author
  • Belinda Kingston
    • 2
    Email author
  • Judy King
    • 3
  • Arshi Denton
    • 4
  • Simon Waters
    • 5
  • Ailsa Sita-Lumsden
    • 6
  • Farah Rehman
    • 6
  • Chara Stavraka
    • 7
  • Hartmut Kristeleit
    • 7
  • Elinor Sawyer
    • 7
  • David Houghton
    • 8
  • Neville Davidson
    • 8
  • Sacha Howell
    • 9
  • Julia Choy
    • 10
  • Peter Harper
    • 10
  • Rebecca Roylance
    • 11
  • Raja Fharat
    • 12
  • Kabir Mohammed
    • 13
  • Alistair Ring
    • 1
  • Stephen Johnston
    • 2
  1. 1.Department of Medicine, Breast UnitThe Royal Marsden NHS Foundation TrustSuttonUK
  2. 2.Department of Medicine, Breast UnitThe Royal Marsden NHS Foundation TrustLondonUK
  3. 3.Royal Free Hospital NHS Foundation TrustLondonUK
  4. 4.Mount Vernon Cancer Centre and London North West University Healthcare NHS TrustNorthwoodUK
  5. 5.Velindre Cancer CentreCardiffUK
  6. 6.Imperial College Healthcare NHS TrustLondonUK
  7. 7.Department of Medical OncologyGuy’s and St Thomas’ NHS Foundation TrustLondonUK
  8. 8.Ramsay Healthcare UK -Rivers HospitalSawbridgeworthUK
  9. 9.The Christie NHS Foundation TrustManchesterUK
  10. 10.Leaders in Oncology CareHCA HealthcareLondonUK
  11. 11.Hospitals Biomedical Research CentreNIHR University College London, University College London Hospitals NHS Foundation TrustLondonUK
  12. 12.University College London Hospitals NHS Foundation TrustLondonUK
  13. 13.Research and Development DepartmentThe Royal Marsden NHS Foundation TrustSuttonUK

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